General Information

Nearly half of the human genome is made of Transposable Elements (TEs) and, although the vast majority of them are unable to mobilize, a significant proportion is transcribed especially in pluripotent stem cells and in certain pathologies. While the mobility of TEs is generally considered detrimental to the host, their accumulation in the genome provides a source of genetic material that has co-opted during evolution to benefit various cellular functions, including those related to embryogenesis. In my lab I intend to dissect what are the functions of TE-derived RNAs, especially endogenous retroviruses that are transcribed during early embryogenesis in a stage-specific manner, and the impact their dysregulation has on different pathologies. The research lines are:

  • Identification of new functions of endogenous retroviruses during development using zebrafish as a model.
  • Role of human specific endogenous retroviruses during embryonic development (HERVs) and in developmental pathologies (22q11 deletion syndrome; 22qDS) using genome-edited hESCs.
  • Analysis of the IFN response activation mediated by TEs in rare diseases and age-associated diseases.
Scientific Impact

Both the functions of TEs during embryonic development and the activation of the major antiviral innate immune pathway, the type I interferon (IFN) response, by endogenous TE expression, has emerged as a new and exciting field in biomedicine being documented by the more prestigious journals in the last few years. However, there is controversy regarding the type of TEs and the biological functions they have at different developmental stages, as well as the nature of the TE-derived nucleic acids responsible for stimulating IFN production in such important pathological processes as cancer, senescence and autoimmune diseases.
Therefore, implementing and developing experimental and computational approaches to analyze the molecular mechanisms underlying the functions of TEs will provide wholly new perspectives to our understanding of various diseases.

Social Impact

Haploinsufficiency of DGCR8 contributes to the human 22q11.2DS, whereas mutations inactivating DGCR8 function are considered drivers of tumors, including the pediatric Wilm’s tumor. This research line could identify new therapeutic targets leading to the development of treatments for patients with 22q11DS. In addition, I am the director of the “Aula de Estudios del Síndrome de deleción 22q11.2” which ensures the transfer of the knowledge generated to the Society. On the other hand, considering that TEs can activate the interferon
response in tumor cells and age-related diseases, our research could provide new therapeutic target for some types of tumors and for alleviating human aging-related disorders. Finally, I am a member of the EU-funded Andalucía Biotec Salud Biomodels Platform, which aims to develop disease diagnostic tools and advanced therapies.

Activities to Strengthen the Strategic Line

Apply for ERC Synergy Grant (EU) in collaboration on the dual role of TEs on miRNA synthesispathway mutations-driven tumors: impact of insertions vs IFN  activation.

Members
Researchers - R3
Postdoctoral Researchers - R2
Predoctoral Researchers - R1
Projects
Publications